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Öğe Idarubicin versus daunorubicin versus mitoxantrone for induction chemotherapy in acute myeloid leukemia: Patient registration study of Turkish society of hematologyacute myeloid leukemia working group(American Society of Hematology, 2023) Pınar, İbrahim Ethem; Çelik, Serhat; Polat, Merve Gökçen; Karataş, Aylin Fatma; Doğan, Ali; Iltar, Utku; Cengiz Seval, Güldane; Sevindik, Ömür GökmenIntroduction: Standard induction chemotherapy in newly diagnosed acute myeloid leukemia (AML) includes a combination of standard-dose cytarabine and an anthracycline (idarubicin [IDA], daunorubicin [DNR], or mitoxantrone [MXR]). Anthracycline selection is still not standardized, and the impact of anthracycline selection on survival and response in patients with adverse genetic risk is of interest. The study aimed to retrospectively compare the effectiveness of induction regimens with respect to anthracycline preference. Methods: The study population was recruited from the Turkish AML Registry project database based on documentation of newly diagnosed AML and induction chemotherapy with IDA, DAU, or MXR in combination with cytarabine. Patients diagnosed before 31 August 2022 were received typical “7 + 3” induction chemotherapy containing 3 days of IDA, DAU, or MXR. Results: The study included 317 newly diagnosed AML patients (median age 51; range, 18 - 79; 55.2% male). Of the patients, IDA was administered in 266 (83.9%), DNR in 42 (13.2%), and MXR in 9 (2.8%). The three anthracycline treatment groups were similar between age, gender, type of AML by the World Health Organization (WHO), and risk classification by 2017 European LeukemiaNet (ELN) when evaluated according to the baseline disease characteristics. At the time of diagnosis, although the median white blood cell levels were 19 x 10 9/L (0.4 - 355) in the IDA, 7.8 x 10 9/L (0.7 - 357.2) in the DAU, and 5.5 x 10 9/L (0.6 - 34) in the MXR therapy group (p = 0.019); the hemoglobin and platelet levels and bone marrow blast percentage were similar between the treatment groups. FMS-like tyrosine kinase-3 internal tandem duplication ( FLT3-ITD) (p = 0.561) and Nucleophosmin 1 gene ( NPM1) (p = 0.430) mutation frequencies were also similar between treatment groups. Morphological complete remission (CR) was documented in 65% of all evaluable patients. Among the patient groups, CR was 67.7% for IDA, 50% for DNR, and 55.6% for MXR (p = 0.081). In univariate analysis (Table 1), significant predictors of overall survival (OS) were age ?60 years (p <0.001), acute leukemias of ambiguous lineage (p <0.001), presence of disseminated intravascular coagulation (DIC) (p = 0.012), and FLT3-ITD mutation (p = 0.018); no significant interaction was noted between NPM1 mutation and OS (p = 0.059). Additionally, when idarubicin was taken as a reference, there was no meaningful relationship between anthracycline type and OS (p values for daunorubicin and mitoxantrone were 0.145 and 0.356, respectively). In multivariate analysis (Table 1), age ?60 years (p = 0.001), acute leukemias of ambiguous lineage (p = 0.007), and the presence of DIC (p = 0.040) remained significant. After a median follow-up of 29.8 months, 32.5% relapse cases were documented and similarly distributed among IDA (33.1%), DNR (31%), and MXR (22.2%) therapy groups (p = 0.771). During the same period, allogeneic hematopoietic stem cell transplantation (AHSCT) was documented in 10.9% and 26.2% of patients treated for IDA and DNR, respectively. No patient progressed to AHSCT in the MXR arm (p <0.001). In the study, 142 (44.8%) deaths were reported, and there was a 48.5%, 26.2%, and 22.2% mortality rate between the IDA, DNR, and MXR treatment groups, respectively. There was no significant difference in OS by anthracycline type in both the study cohort and age group <60 years (Figures 1A and 1B). There was also no significant difference in OS in patients with the adverse genetic risk group and <60 years age group with adverse genetic risk, according to 2017ELN (Figures 1C and 1D). The results may have been influenced by the number of patients in the treatment groups of the retrospective study and by differences in fitness levels that needed to be measured systematically. Conclusions: We are encouraged that our findings mostly agree with previously published studies and that IDA, DNR, and MXR offer comparable survival values in the research and the younger patient groups. In the future, the ever-changing treatment environment in patient groups with targetable mutations makes choosing the optimal anthracycline for induction chemotherapy in AML much more difficult.Öğe Prospective real-world outcomes of acute myeloid leukemia(American Society of Hematology, 2023) Karakuş, Volkan; Iltar, Utku; Yenihayat, Emel Merve; Polat, Merve Gökçen; Çelik, Serhat; Malkan, Ümit Yavuz; Cengiz Seval, Güldane; Alacacıoğlu, İnciBackground: It is evident that treatment outcomes improve with the clinical studies, in this study we aimed to investigate the demographics and treatment modalities of the acute myeloid leukemia (AML) patients in a large population-based cohort who were diagnosed and followed up in Turkey as a real-world data. Methods: All AML adult patients who were recorded on the database of Turkish AML Registry project from 25 sites were included in this study if they were diagnosed before 1st of June 2022. Study approved by ethics committee and Ministry of Health of Turkey. Demographics and disease related parameters both at the time of diagnosis and at the follow up and treatment outcomes were presented. Results: A total of 906 patients were included in the study, 891 patients data accepted as adequate and underwent further evaluation. Median follow-up period was 12.0 (SD:26.6) months and 45.4% of the patients were female. Median age at the time of diagnosis was 58 (18-91). According to the FAB classification most common subtypes were M4 (23.6%), M2 (21.6%), M5 (16.8%) and M1 (13.5%) and AML, NOS (36.9%) is the most common type according to the WHO classification. Of the patients 60.8%, 24.7%, 14.5%, was intermediate, favorable and poor respectively considering AML risk stratification (ELN 2017) by genetics. Only 4.4% of the patients had extramedullary involvement. For the first induction 70.8% of the patients had received intensive regimens composing anthracyclines and ARA-C and for the first relapse 71.8%. ARA-C (71.7%) backbone and Azacitidine alone (13.4%) are the most used regimens, 10.5% and 22.5% underwent allo-HCT during the first and second induction respectively. Response rates obtained by the induction therapies were as follows; 61.7% CR (including 9.3% MLFS), 14.2% PR, 8.6% SD, 15.5% PD, the ratio was 59.7% and 24.3% for CR2 and PD respectively. Median overall survival has not been reached for the favorable risk group, were 16.2 months for the intermediate risk and 14.1 months for the poor risk group (p<0.001) and 22.7 months for the entire population. Median progression free survival were 32.6 months for the favorable risk group, 12.7 months for the intermediate risk and 9.4 months for the poor risk group (p<0.001) and 15.2 months for the entire population (Figure 1). COX regression analysis were performed for the prognostic factors of OS, univariate analysis performed with the parameters; age (<60 and ?60), FAB classification, ECOG, FLT3, NMP1, HCT were accepted as clinically significant covariates. First univariate then with the significant parameters (p<0.05) multivariate COX regression analysis were perfomed. With the multivariate analysis age (p:0.005, HR:2.140, 95% CI: 1.254-3.653), FAB classification (favorable were reference, intermediate p:0.045, HR: 2.269, 95% CI: 1.017-5.064, poor p:0.217, HR: 2.105, 95% CI: 6.858) and HCT (p:0.034, HR:2.618, 95% CI: 1.073-6.387) were found as significant. Conclusion: Progression free survival obtained after induction therapy and overall survival were relatively shorter than the ones which were presented by other real-world registries. Lack of early access to the targeted and novel agents, like Flt3 inhibitors, Venetoclax, IDH1 and 2 inhibitors, CPX351 and Glasdegib should be a potential explanation to this relatively short PFS and OS. We have also been aware of un-ideal access to well established and nation wide cytogenetic laboratory service to induce early integration of targeted agents to the treatment and better risk stratification to determine the patients who should obtain the best prolonged survival via allo-HCT.











